Preliminary observations suggest that certain unusual findings may be seen on neurologic, immunologic and virologic examination of patients with "chronic fatigue syndrome (CFS)". CFS is a cyclic chronic illness characterized by profound, disabling fatigue, fever, myalgias, arthralgias, pharyngitis, adenopathy, paresthesias, cognitive impairment and other symptoms. Transient neurologic events also are seen: e.g., primary seizures, ataxia, blindness, and paresis. Especially in these latter patients, the diagnosis of multiple sclerosis (MS) is considered. The first objective of the study is to distinguish 25 patients with CFS from 25 patients with MS, and from 25 healthy subjects, all matched for age and sex, through detailed clinical, neurologic, immunologic and virologic evaluation. Neurologic evaluation would include a neurologic examination, evoked potentials, lumbar puncture, neuropsychologic testing of mood and cognition, and magnetic resonance imaging (MRI) of the brain and skeletal muscle. Immunologic studies would include the use of monoclonal antibodies, flow cytometry and conventional functional assays to examine the phenotype and function of spinal fluid lymphocytes, peripheral blood natural killer or NK cells; isolation and enumeration of B-cells including determination of the phenotypic stage of differentiation in ontogeny and examination of the responses of resting and activated B-cell subsets to various signals of activation; measurement of T-cell subsets, including recently-described CD4 subsets which are inducers of help and inducers of suppression, as well as measurement of T-cell function by a variety of techniques; and studies of various cytokines, including IL-1 beta, IL-2, tumor necrosis factor, IF-gamma and IF-alpha 2. Virologic studies would include serologic studies of all human herpesviruses, including the recently-discovered lymphotropic and neurotropic human herpesvirus 6. A second objective of the study is to relate the cyclic clinical course of illness in patients with CFS to the various neurologic, immunologic and virologic parameters described above. By conducting serial longitudinal studies, we hope to identify neuroimmunological features which worsen and improve in conjunction with clinical exacerbation and remission. By conducting simultaneous batteries of neurologic, immunologic and virologic studies at the same point in time we hope to identify possible interrelationship between the various neuroimmunological and virological parameters.